African Americans are >60% more likely to develop and >200% more likely to die from prostate cancer than their Caucasian counterparts. It is known that African Americans are more likely to have inflammation in their prostate biopsy specimens, and tend to have higher levels of androgens in blood than Caucasians. Therefore, we hypothesize that inflammation and androgens metabolism may play critical roles in prostate cancer disparity. We plan to test our hypotheses with the following three Specific Aims: 1) To study whether p-arrestin may contribute to prostate cancer disparity by modulating CXCR2-mediated angiogenesis and metastasis of prostate cancer (PI: Richardson). 2) To determine whether expression and regulation of AloxS and bltl by promoter methylation and polymorphism may contribute to prostate cancer disparity between African American and Caucasian men (PI: Chen). 3) To determine whether polymorphisms of UGT2B genes may contribute to prostate cancer development and disparity (PI: Grant). This project is a multi-Pi and multi-disciplinary study which incorporates expertise of three laboratories to study molecular mechanism of prostate cancer disparity. We expect to define the roles of inflammation and androgen metabolism in prostate cancer disparity.